Trial document




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  DRKS00011156

Trial Description

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Title

Phase III, Randomized, Double-Blind, Multicentre Clinical Trial on Clinical Efficacy and Safety of Platelet Concentrates Treated with the THERAFLEX UV-Platelets Procedure in Comparison to Conventional Platelet Components.

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

Photodynamic and photochemical pathogen inactivation are promising new techniques developed to improve the safety of blood products. The UVC irradiation procedure using the Theraflex UV system is intended to reduce the risk of platelet transfusion transmitted infectious diseases like viruses, bacteria and protozoa in conventional human platelet concentrates (PCs). Pathogen inactivation is performed by irradiation of the PCs with UVC light without using photoactive reagents. Leukocytes will also be inactivated by the UVC-treatment, therefore no additional gamma-irradiation for the prevention of a donor cell versus recipient disease, called transfusion-associated graft versus host disease (TA-GvHD), is required.
The aim of this clinical trial is to evaluate the efficacy and safety of UVC-treated platelet concentrates (UVC-PC) in comparison to control PCs which are commonly used for the treatment of patients with thrombozytopenia (untreated PC and PC treated with gamma-irradiation).
166 Patients with hematologic or oncologic diseases with thrombocytopenia will be enrolled into the clinical trial and randomized into two groups. Neither the investigator nor the patient will know which type of PC (UVC-PC or untreated PC) is used for transfusion in order to avoid any bias due to knowledge of the type of PC. The clinical trial is subdivided into 3 main phases; the screening phase for the selection of patients fulfilling the eligibility criteria, a treatment phase over a maximum of 28 days, in which patients will be treated with a maximum of 8 PCs, and a safety-follow-up period, during which the occurrence of any adverse event will be documented.
For the determination of the efficacy of UVC-PCs, the increase of platelets in patient’s blood will be measured 1 and 24h after transfusion of the PC, whereby the number of transfused platelets and the body surface area of the patients will be taken into account. This laboratory value is called corrected count increment (CCI). The CCI is a surrogate marker and will be used as parameter for determination of the efficacy of the treatment with UVC-PCs.
Safety and tolerance is assessed by measuring relevant laboratory and vital parameters, testing for antibodies against UVC-irradiated platelets and documenting any adverse events.

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Brief Summary in Scientific Language

Photodynamic and photochemical pathogen inactivation are promising new techniques developed to improve the safety of blood products. The UVC irradiation procedure using the Theraflex UV system is intended to reduce the risk of platelet transfusion transmitted infectious diseases like viruses, bacteria and protozoa in conventional human, plasma reduced, leukocyte depleted platelet concentrates (PCs).
The UVC-procedure for the pathogen inactivation of plasma-reduced PCs was developed on the basis of UVC irradiation. It inactivates pathogens mainly by direct interaction with nucleic acids (RNA and DNA), resulting in the formation of cyclobutane pyrimidine and pyrimidine pyrimidone dimers that prevent the elongation of nucleic acid transcripts. The pathogen reduction system works without the addition of a potentially toxic photoactive substances or new ingredients. Residual leukocytes remaining in the product after leukodepletion will be inactivated by the UVC treatment , therefore no further prophylaxis for transfusion associated graft versus host disease (TA-GvHD) is required.
In this double blinded clinical trial 166 Patients with hematologic or oncologic diseases will be randomized into two groups. The primary objective of the trial is to demonstrate the non-inferiority of UVC-treated plasma reduced platelet concentrates (UVC-PCs) in comparison to untreated plasma reduced platelet concentrates (Control-PCs) stored for up to 5 days in adult patients with hematologic or oncologic diseases and thrombocytopenia based on the 1 hour CCI of not more than 30% below the control.
As secondary safety parameters the incidence of WHO grade 3 and 4 bleeding events, frequency of patients with clinical refractoriness to PLTs and proportion of patients with clinical refractoriness to PLTs with serologic conversion to positive tests for HLA and/or HPA alloantibodies or UVC-related neoantigens, frequency of alloimmunization to UVC-related neoantigens on PLTs (all patients) and rate of adverse events and serious adverse events will be evaluated.

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Organizational Data

  •   DRKS00011156
  •   2016/10/04
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  •   no
  •   Approved
  •   365/15, Ethikkommission des Fachbereichs Humanmedizin der Johann-Wolfgang-Goethe-Universität Frankfurt am Main
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Secondary IDs

  •   2015-001035-20 
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Health Condition or Problem studied

  •   D69.6 -  Thrombocytopenia, unspecified
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Interventions/Observational Groups

  •   UVC-treated plasma reduced leukodepleted platelet concentrates (UVC PC) stored in SSP+ additive solution. Each Patient will be treated with a maximum of 8 PCs within 28 days.
  •   Untreated plasma reduced leukodepleted platelet concentrates (Control-PC) stored in SSP+ additive solution. Control PCs will be gamma-irradiated with 30 Gy if a TA-GvHD prophylaxes is required. Each Patient will be treated with a maximum of 8 PCs within 28 days.
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist, caregiver, assessor
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   II-III
  •   N/A
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Primary Outcome

The primary objective of the trial is to demonstrate the non-inferiority of UVC-treated plasma reduced platelet concentrates (UVC-PCs) in comparison to untreated plasma reduced platelet concentrates (Control-PCs) stored for up to 5 days in adult patients with hematologic or oncologic diseases and thrombocytopenia based on the 1 hour CCI of not more than 30% below the control. The CCI will be calculated using the following formula:



CCI=(Post-pre count (×10E9⁄L)) /(Platelet dose transfused (× 10E11) × BSA*

* BSA: Body Surface Area

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Secondary Outcome

To compare the post-transfusion PLT recovery, measured by platelet count increments (24 hour CCI, 1 hour and 24 hour CI) between treatment groups*;
To compare PLT and RBC transfusions support between treatment groups*;
Rate of bleeding ≥ WHO grade 3 and grade 4*;
Rate of clinical refractoriness defined as two consecutive transfusions with a 1 hour CCI < 7.5*;
Rate of immunologic refractoriness defined as two consecutive transfusions with a 1 hour CCI < 7.5 and serologic conversion to positive tests for HLA and/or HPA alloantibodies or for antibodies to UVC-related neoantigens*;
Frequency of alloimmunization to UVC-related neoantigens on PLTs**;
Rate of adverse events (AEs) and seriousb adverse events (SAE)**.


*assessed during treatment period only; **assessed during treatment and follow-up periods;

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • other 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
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Recruitment

  •   Actual
  •   2016/10/06
  •   166
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

Patients with hematologic or oncologic diseases with thrombocytopenia or expected to become thrombocytopenic after chemotherapy or due to underlying active disease;
Expected to receive ≥ 1 PLT transfusions during their hospital stay; Age ≥ 18 years;
Written Informed Consent; Life expectancy ≥ 8 weeks;
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

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Exclusion Criteria

Known immunological refractoriness to PLT transfusions, i.e. HLA and/or HPA alloimmunization (documented in the patient’s medical record);
History or diagnosis of an autoimmune disease affecting haemostasis;
Acute or chronic disseminated intravascular coagulation (DIC);
History or diagnosis of thrombotic thrombocytopenic purpura or haemolytic uremic Syndrome;
Positive serum or urine pregnancy test;
Lactation;
Simultaneous participation in another interventional trial with non-approved drugs;
Previous inclusion in this trial;
Acute promyelocytic leukemia (AML, FAB subtype M3);
Active bleeding ≥ WHO Grade 3 at time of enrolment requiring one or more RBC transfusions and/or therapeutic PLT transfusions;
Splenomegaly defined as a palpable spleen felt more than 4 cm below costal margin;
History of severe anaphylactic transfusion reaction (i.e. patients requiring washed PLTs due to known severe allergic reaction to plasma proteins);
Legal incapacity or other circumstances preventing the patient from understanding the nature, meaning and implications of the clinical trial. (e.g. not able to read and understand German language);
Severe uncontrolled infection;
History of severe vaginal bleeding due to myoma.

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Addresses

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    • Blutspendedienst der Landesverbände des Deutschen Roten Kreuzes Niedersachsen, Sachsen-Anhalt, Thüringen, Oldenburg und Bremen gGmbH (DRK-BSD NSTOB)
    • Eldagsener Str. 38
    • 31832  Springe
    • Germany
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    • DRK-Blutspendedienst NSTOB, Institut Springe
    • Mr.  Prof.  Axel  Seltsam 
    • Eldagsener Str. 38
    • 31832  Springe
    • Germany
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    • DRK-Blutspendedienst NSTOB
    • Mr.  Prof.  Axel  Seltsam 
    • Eldagsener Str.38
    • 31832  Springe
    • Germany
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Sources of Monetary or Material Support

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    • Blutspendedienste des Deutschen oder Bayerischen Roten Kreuzes, vertreten durchDRK-BSD-NSTOB
    • Eldagsenerstr.38
    • 31832  Springe
    • Germany
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    • Macop Pharma S.A.S.
    • Rue Lorthiois
    • 59420  Mouvaux
    • France
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Status

  •   Recruiting complete, follow-up complete
  •   2019/03/11
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.